Apparently, the activity of Gli can be adversely affected by tumor suppressors (p53, NUMB, SNF5) [147–149], MAPKKK/MEKK [150, 151], and miRNAs (miR-324-5p, miR-361, miR-326) [152–154] in Smo-independent Hh signaling appear to be a fallback activation pathway in canonical Hh signaling and a way for cells to evade the classical Hh pathway to activate downstream gene expression in response to abnormal environmental stress. Here, GLI1 is linked to neoplasm.